7VNH

drosophlia AHR PAS-B domain bound by the antagonist alpha-naphthoflavone

Summary for 7VNH

• Entry DOI: 10.2210/pdb7vnh/pdb
• Descriptor: Ahr homolog spineless, 2-PHENYL-4H-BENZO[H]CHROMEN-4-ONE (3 entities in total)
• Functional Keywords: transcription factor, ligand binding domain, transcription
• Biological source: Drosophila melanogaster (Fruit fly)
• Total number of polymer chains: 2
• Total formula weight: 28167.96

Authors

Dai, S.Y. (deposition date: 2021-10-11, release date: 2022-04-13, Last modification date: 2023-11-29)

Primary citation

Dai, S.,Qu, L.,Li, J.,Zhang, Y.,Jiang, L.,Wei, H.,Guo, M.,Chen, X.,Chen, Y.
Structural insight into the ligand binding mechanism of aryl hydrocarbon receptor.
Nat Commun, 13:6234-6234, 2022

PubMed Abstract: The aryl hydrocarbon receptor (AHR), a member of the basic helix-loop-helix (bHLH) Per-Arnt-Sim (PAS) family of transcription factors, plays important roles in regulating xenobiotic metabolism, cellular differentiation, stem cell maintenance, as well as immunity. More recently, AHR has gained significant interest as a drug target for the development of novel cancer immunotherapy drugs. Detailed understanding of AHR-ligand binding has been hampered for decades by the lack of a three-dimensional structure of the AHR PAS-B domain. Here, we present multiple crystal structures of the Drosophila AHR PAS-B domain, including its apo, ligand-bound, and AHR nuclear translocator (ARNT) PAS-B-bound forms. Together with biochemical and cellular assays, our data reveal structural features of the AHR PAS-B domain, provide insights into the mechanism of AHR ligand binding, and provide the structural basis for the future development of AHR-targeted therapeutics.

PubMed: 36266304
DOI: 10.1038/s41467-022-33858-w

Experimental method

X-RAY DIFFRACTION (2.402 Å)